Final Research Plan

Final Research Plan for Hepatitis C Virus Infection in Adolescents and Adults: Screening

Recommendations made by the USPSTF are independent of the U.S. government.
They should not be construed as an official position of the Agency for Healthcare
Research and Quality or the U.S. Department of Health and Human Services.

The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from September 21 until October 18, 2017 at 5:00 p.m., ET.

Analytic Framework

* Includes persons without known liver function test abnormalities. Adolescents are defined as those ages 12 to 17 years. Excludes persons living with HIV, transplant recipients, and patients with renal failure.† Defined as HCV antibody testing with confirmatory HCV RNA testing as indicated.‡ Includes interventions that may affect vertical transmission of HCV, such as cesarean delivery, amniocentesis, and fetal monitoring, as well as antiviral treatment.

Key Questions to Be Systematically Reviewed

1a. Does screening for hepatitis C virus (HCV) infection in pregnant and nonpregnant adolescents and adults without known abnormal liver enzyme levels reduce HCV-related mortality and morbidity or affect quality of life?
1b. Does prenatal screening for HCV infection reduce risk of vertical transmission of HCV infection?
2. What is the effectiveness of different risk- or prevalence-based methods for screening for HCV infection on clinical outcomes?
3. What is the yield (number of new diagnoses per tests performed) of one-time versus repeat screening for HCV infection, and how does the screening yield vary in different risk groups?
4. What are the harms of screening for HCV infection (e.g., anxiety and labeling)?
5. What are the effects of interventions during labor and delivery or the perinatal period on risk of vertical transmission of HCV infection?
6. What is the effectiveness of currently recommended antiviral treatments in improving health outcomes in patients with HCV infection?*
7. What is the effectiveness of currently recommended antiviral treatments in achieving a sustained virologic response in patients with HCV infection?*
8. What are the harms of currently recommended antiviral treatments?*
9. What is the association between improvement of sustained virologic response following antiviral treatment and reduction in risk of HCV-related adverse health outcomes?

Contextual Questions

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

Based on population level estimates, what are recent trends in the epidemiology, prevalence, and incidence of HCV infection in the United States, including in primary care settings, over the past 5 to 10 years?

What are the effects of different risk- or prevalence-based methods for screening for HCV infection in modeling studies?

What is the effect of antiviral treatments on behavioral outcomes?

Research Approach

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the KQs.

The evidence review will focus on screening in asymptomatic persons without known liver function test abnormalities. Patients who are coinfected with the hepatitis B virus or HIV will be excluded from the review, since management of these conditions may include evaluation for HCV infection. Older antiviral regimens that are no longer recommended will also be excluded. For KQs related to screening, the focus will be on settings applicable to U.S. primary care and emergency departments. Studies of screening conducted in specialty settings and geographic areas in which the epidemiology and management of HCV infection differ substantially from U.S. primary care settings will be excluded.

Persons with screen-detected or asymptomatic HCV infection (patients with a METAVIR fibrosis stage of 0–3, if symptom status is not reported); persons with no prior antiviral treatment; includes pregnant women

Persons who are coinfected with the hepatitis B virus or HIV, transplant patients, persons with renal failure

Interventions

Currently recommended direct-acting antiviral regimens

Interferon-based treatment and other nonrecommended regimens

Comparisons

Another direct-acting antiviral regimen or older antiviral regimen; includes clinical trials without a comparison group

Response to Public Comment

The draft Research Plan was posted for comment on the USPSTF Web site from September 21, 2017 through October 18, 2017. After reviewing public comments, the USPSTF revised the Research Plan to clarify the following: screening settings include emergency departments and settings that offer integrated services for primary care and behavioral health care; subpopulations of interest include drug use, persons using medication-assisted therapies, and nonpregnant women of childbearing age; morbidity outcomes include extrahepatic manifestations of HCV infection, such as depression and diabetes; health outcomes include perinatal HCV transmission; and the population for antiviral treatment includes persons with a METAVIR fibrosis stage of 0 to 3. The USPSTF also added a KQ on the yield of repeat HCV screening and revised Contextual Question 3 to address the effects of antiviral treatment on both positive and negative behaviors pertaining to HCV risk.